Dataset Information

GFR estimated with creatinine rather than cystatin C is more reflective of the true risk of adverse outcomes with low GFR in kidney transplant recipients.

ABSTRACT:

Background

Serum cystatin C-based estimated glomerular filtration rate (eGFRcys) generally associates with clinical outcomes better than serum creatinine-based eGFR (eGFRcr) despite similar precision in estimating measured GFR (mGFR). We sought to determine whether the risk of adverse outcomes with eGFRcr or eGFRcys was via GFR alone or also via non-GFR determinants among kidney transplant recipients.

Methods

Consecutive adult kidney transplant recipients underwent a standardized GFR assessment during a routine follow-up clinic visit between 2011 and 2013. Patients were followed for graft failure or the composite outcome of cardiovascular (CV) events or mortality through 2020. The risk of these events by baseline mGFR, eGFRcr and eGFRcys was assessed unadjusted, adjusted for mGFR and adjusted for CV risk factors.

Results

There were 1135 recipients with a mean baseline mGFR of 55.6, eGFRcr of 54.8 and eGFRcys of 46.8 ml/min/1.73 m2 and a median follow-up of 6 years. Each 10 ml/min/1.73 m2 decrease in mGFR, eGFRcr or eGFRcys associated with graft failure [hazard ratio (HR) 1.79, 1.68 and 2.07, respectively; P < .001 for all) and CV events or mortality outcome (HR 1.28, 1.19 and 1.43, respectively; P < .001 for all). After adjusting for mGFR, eGFRcys associated with graft failure (HR 1.57, P < .001) and CV events or mortality (HR 1.49, P < .001), but eGFRcr did not associate with either. After further adjusting for CV risk factors, risk of these outcomes with lower eGFRcys was attenuated.

Conclusion

eGFRcr better represents the true relationship between GFR and outcomes after kidney transplantation because it has less non-GFR residual association. Cystatin C is better interpreted as a nonspecific prognostic biomarker than is eGFR in the kidney transplant setting.

SUBMITTER: Keddis MT

PROVIDER: S-EPMC10387404 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature

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Publications

GFR estimated with creatinine rather than cystatin C is more reflective of the true risk of adverse outcomes with low GFR in kidney transplant recipients.

Keddis Mira T MT Howard Matthew R MR Galapia Leyton L Barreto Erin F EF Zhang Nan N Butterfield Richard J RJ Rule Andrew D AD

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 20230701 8

<h4>Background</h4>Serum cystatin C-based estimated glomerular filtration rate (eGFRcys) generally associates with clinical outcomes better than serum creatinine-based eGFR (eGFRcr) despite similar precision in estimating measured GFR (mGFR). We sought to determine whether the risk of adverse outcomes with eGFRcr or eGFRcys was via GFR alone or also via non-GFR determinants among kidney transplant recipients.<h4>Methods</h4>Consecutive adult kidney transplant recipients underwent a standardized ...[more]

PMID: 36646435

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Project description:Background and objectiveseGFR equations have been evaluated in kidney transplant recipients with variable performance. We assessed the performance of the Modification of Diet in Renal Disease equation and the Chronic Kidney Disease Epidemiology Collaboration equations on the basis of creatinine, cystatin C, and both (eGFR creatinine-cystatin C) compared with measured GFR by iothalamate clearance and evaluated their non-GFR determinants and associations across 15 cardiovascular risk factors.Design, setting, participants, & measurementsA cross-sectional cohort of 1139 kidney transplant recipients >1 year after transplant was analyzed. eGFR bias, precision, and accuracy (percentage of estimates within 30% of measured GFR) were assessed. Interaction of each cardiovascular risk factor with eGFR relative to measured GFR was determined.ResultsMedian measured GFR was 55.0 ml/min per 1.73 m(2). eGFR creatinine overestimated measured GFR by 3.1% (percentage of estimates within 30% of measured GFR of 80.4%), and eGFR Modification of Diet in Renal Disease underestimated measured GFR by 2.2% (percentage of estimates within 30% of measured GFR of 80.4%). eGFR cystatin C underestimated measured GFR by -13.7% (percentage of estimates within 30% of measured GFR of 77.1%), and eGFR creatinine-cystatin C underestimated measured GFR by -8.1% (percentage of estimates within 30% of measured GFR of 86.5%). Lower measured GFR associated with older age, women, obesity, longer time after transplant, lower HDL, lower hemoglobin, lower albumin, higher triglycerides, higher proteinuria, and an elevated cardiac troponin T level but did not associate with diabetes, smoking, cardiovascular events, pretransplant dialysis, or hemoglobin A1c. These risk factor associations differed for five risk factors with eGFR creatinine, six risk factors for eGFR Modification of Diet in Renal Disease, ten risk factors for eGFR cystatin C, and four risk factors for eGFR creatinine-cystatin C.ConclusionsThus, eGFR creatinine and eGFR creatinine-cystatin C are preferred over eGFR cystatin C in kidney transplant recipients because they are less biased, more accurate, and more consistently reflect the same risk factor associations seen with measured GFR.

Project description:Rationale & objectiveUse of cystatin C in addition to creatinine to estimate glomerular filtration rate (estimated glomerular filtration rate based on cystatin C [eGFRcys] and estimated glomerular filtration rate based on creatinine [eGFRcr], respectively) is increasing. When eGFRcr and eGFRcys are discordant, it is not known which is more accurate, leading to uncertainty in clinical decision making.Study designCross-sectional analysis.Setting & participantsFour thousand fifty participants with measured glomerular filtration rate (mGFR) from 12 studies in North America and Europe.ExposuresSerum creatinine and serum cystatin C.OutcomesPerformance of creatinine-based and cystatin C-based glomerular filtration rate estimating equations compared to mGFR.Analytical approachWe evaluated the accuracy of eGFRcr, eGFRcys, and the combination (eGFRcr-cys) compared to mGFR according to the magnitude of the difference between eGFRcr and eGFRcys (eGFRdiff). We used CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equations to estimate glomerular filtration rate. eGFRdiff was defined as eGFRcys minus eGFRcr and categorized as less than -15, -15 to <15, and ≥15 mL/min/1.73 m2 (negative, concordant, and positive groups, respectively). We compared bias (median of mGFR minus eGFR) and the percentage of eGFR within 30% of mGFR.ResultsThirty percent of participants had discordant eGFRdiff (21.0% and 9.6% negative and positive eGFRdiffs, respectively). In the concordant eGFRdiff group, all equations displayed similar accuracy. In the negative eGFRdiff groups, eGFRcr had a large overestimation of mGFR (-13.4 [-14.5 to -12.2] mL/min/1.73 m2) and eGFRcys had a large underestimation (9.9 [9.1-11.2] mL/min/1.73m2), with opposite results in the positive eGFRdiff group. In both negative and positive eGFRdiff groups, eGFRcr-cys was more accurate than either eGFRcr or eGFRcys. These results were largely consistent across age, sex, race, and body mass index.LimitationsFew participants with major comorbid conditions.ConclusionsDiscordant eGFRcr and eGFRcys are common. eGFR using the combination of creatinine and cystatin C provides the most accurate estimates among persons with discordant eGFRcr or eGFRcys.

Project description:Rationale & objectiveSerum creatinine and cystatin C are used to estimate glomerular filtration rate, but creatinine-based estimated glomerular filtration rate (eGFRcr), cystatin C-based estimated glomerular filtration rate (eGFRcys), and combined creatinine- and cystatin C-based estimated glomerular filtration rate (eGFRcr-cys) are often divergent, particularly in older adults. We investigated which estimated glomerular filtration rate (eGFR) was more accurate and less biased compared with measured glomerular filtration rate (mGFR).Study designA diagnostic test study from the Berlin Initiative Study.Setting & participantsThe study population included 657 individuals aged 70 years or older with iohexol plasma clearance (mGFR) and serum creatinine and cystatin C measurements: 567 community-dwelling participants and 90 with a serum creatinine of ≥1.5 mg/dL.Tests comparedWe defined 3 groups on the basis of the difference eGFRcys - eGFRcr: whether < -5 mL/min/1.73 m2 (lower eGFRcys), within 5 mL/min/1.73 m2 (reference), or ≥ 5 mL/min/1.73 m2 (lower eGFRcr). eGFRcr, eGFRcys, and eGFRcr-cys were compared to mGFR to assess bias and accuracy.OutcomeMedian bias (eGFR minus mGFR) with 95% CIs and accuracy (percentage of eGFR values within ±30% of mGFR).ResultsThe mean ± standard deviation age was 78 ± 6 years; the mean eGFRcys, eGFRcr, and eGFRcr-cys were 59 ± 23, 64 ± 20, and 61 ± 22 mL/min/1.73 m2, respectively, and the mean mGFR was 56 ± 19 mL/min. Half of the participants were in the lower eGFRcys group (n=337, 51%). Among them, the median bias for eGFRcys was the lowest (median bias, -2.7; 95% CI, -3.8 to -1.9) compared with the other eGFR equations. Conversely, in the lower eGFRcr group (n=121, 18%), the median bias for eGFRcr was the lowest compared with those for eGFRcys and eGFRcr-cys (2.9; [95% CI, 0.9-4.8] vs 13.8 [95% CI, 11.4-15.6] and 9.5 [95% CI, 7.7-11.0], respectively). Accuracy (percentage of eGFR values within ±30% of mGFR) was 93% for eGFRcr in the lower eGFRcr group and 92% for eGFRcys and 94% for eGFRcr-cys in the lower eGFRcys group.LimitationsUntested generalizability in younger populations.ConclusionsAmong older adults, the lower eGFR between eGFRcys and eGFRcr was a more accurate and less biased estimate of mGFR when comparing the groups.

Project description:Rationale & objectiveLarge differences between estimated glomerular filtration rate (eGFR) based on cystatin C (eGFRcys) and creatinine (eGFRcr) occur commonly. A comprehensive evaluation of factors that contribute to these differences is needed to guide the interpretation of discrepant eGFR values.Study designCohort study.Setting & participants468,969 participants in the UK Biobank.ExposuresCandidate sociodemographic, lifestyle factors, comorbidities, medication usage, and physical and laboratory predictors.OutcomeseGFRdiff, defined as eGFRcys minus eGFRcr, categorized into 3 levels: lower eGFRcys (eGFRdiff, less than -15 mL/min/1.73 m2), concordant eGFRcys and eGFRcr (eGFRdiff, -15 to < 15 mL/min/1.73 m2), and lower eGFRcr (eGFRdiff, ≥15 mL/min/1.73 m2).Analytical approachMultinomial logistic regression models were constructed to identify predictors of lower eGFRcys or lower eGFRcr. We developed 2 prediction models comprising 375,175 participants: (1) a clinical model using clinically available variables and (2) an enriched model additionally including lifestyle variables. The models were internally validated in an additional 93,794 participants.ResultsMean ± standard deviation of eGFRcys was 88 ± 16 mL/min/1.73 m2, and eGFRcr was 95 ± 13 mL/min/1.73 m2; 25% and 5% of participants were in the lower eGFRcys and lower eGFRcr groups, respectively. In the multivariable enriched model, strong predictors of lower eGFRcys were older age, male sex, South Asian ethnicity, current smoker (vs never smoker), history of thyroid dysfunction, chronic inflammatory disease, steroid use, higher waist circumference and body fat, and urinary albumin-creatinine ratio >300 mg/g. Odds ratio estimates for these predictors were largely inverse of those in the lower eGFRcr group. The model's area under the curve was 0.75 in the validation set, with good calibration (1.00).LimitationsLimited generalizability.ConclusionsThis study highlights the multitude of demographic, lifestyle, and health characteristics that are associated with large eGFRdiff. The clinical model may identify individuals who are likely to have discrepant eGFR values and thus should be prioritized for cystatin C testing.

Project description:BackgroundAccurate assessment of kidney function is important for the management of solid-organ transplant recipients. In other clinical populations, glomerular filtration rate (GFR) most commonly is estimated using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) creatinine or the 4-variable MDRD (Modification of Diet in Renal Disease) Study equation. The accuracy of these equations compared with other GFR estimating equations in transplant recipients has not been carefully studied.Study designDiagnostic test study.Setting & participantsSolid-organ transplant recipients longer than 6 months posttransplantation from 5 clinical populations (N=3,622, including recipients of kidney [53%], liver [35%], and other or multiple organs [12%]).Index testEstimated GFR (eGFR) using creatinine-based GFR estimating equations identified from a systematic review of the literature. Performance of the CKD-EPI creatinine and the MDRD Study equations was compared with alternative equations.Reference testMeasured GFR (mGFR) from urinary clearance of iothalamate or plasma clearance of iohexol.MeasurementsError (difference between mGFR and eGFR) expressed as P30 (proportion of absolute percent error <30%) and mean absolute error.ResultsWe identified 26 GFR estimating equations. Mean mGFR was 55.1±22.7 (SD) mL/min/1.73 m(2). P30 and mean absolute error for the CKD-EPI and the MDRD Study equations were 78.9% (99.6% CI, 76.9%-80.8%) for both and 10.6 (99.6% CI, 10.1-11.1) versus 11.0 (99.6% CI, 10.5-11.5) mL/min/1.73 m(2), respectively; these equations were more accurate than any of the alternative equations (P <0.001 for all pairwise comparisons for both measures). They performed better than or as well as the alternative equations in most subgroups defined by demographic and clinical characteristics, including type of transplanted organ.LimitationsStudy population included few nonwhites and people with solid-organ transplants other than liver and kidneys.ConclusionsThe CKD-EPI creatinine and the MDRD Study equations perform better than the alternative creatinine-based estimating equations in solid-organ transplant recipients. They can be used for clinical management.

Project description:Rationale & objectiveLower estimated glomerular filtration rate (eGFR) is associated with heart failure (HF) risk. However, eGFR based on cystatin C (eGFRcys) and creatinine (eGFRcr) may differ substantially within an individual. The clinical implications of these differences for risk of HF among persons with chronic kidney disease (CKD) are unknown.Study designProspective cohort study.Setting & participants4,512 adults with CKD and without prevalent HF who enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study.ExposureDifference in GFR estimates (eGFRdiff; ie, eGFRcys minus eGFRcr).OutcomeIncident HF hospitalization.Analytical approachFine-Gray proportional subhazards regression was used to investigate the associations of baseline, time-updated, and slope of eGFRdiff with incident HF.ResultsOf 4,512 participants, one-third had eGFRcys and eGFRcr values that differed by over 15 mL/min/1.73 m2. In multivariable-adjusted models, each 15 mL/min/1.73 m2 lower baseline eGFRdiff was associated with higher risk of incident HF hospitalization (hazard ratio [HR], 1.20 [95% CI, 1.07-1.34]). In time-updated analyses, those with eGFRdiff less than -15 mL/min/1.73 m2 had higher risk of incident HF hospitalization (HR, 1.99 [95% CI, 1.39-2.86]), and those with eGFRdiff ≥15 mL/min/1.73 m2 had lower risk of incident HF hospitalization (HR, 0.67 [95% CI, 0.49-0.91]) compared with participants with similar eGFRcys and eGFRcr. Participants with faster declines in eGFRcys relative to eGFRcr had higher risk of incident HF (HR, 1.49 [95% CI, 1.19-1.85]) compared with those in whom eGFRcys and eGFRcr declined in parallel.LimitationsEntry into the CRIC Study was determined by eGFRcr, which constrained the range of baseline eGFRcr-but not eGFRcys-values.ConclusionsAmong persons with CKD who have large differences between eGFRcys and eGFRcr, risk for incident HF is more strongly associated with eGFRcys. Diverging slopes between eGFRcys and eGFRcr over time are also independently associated with risk of incident HF.

Project description:BackgroundHigher serum cystatin C level is associated with an increased risk of hip fracture in postmenopausal white women, but there is a paucity of data for men. Whether estimated glomerular filtration rate (eGFR) based on cystatin C (eGFRcys) is superior in predicting hip fracture risk to eGFR based on creatinine (eGFRcr) or the combination (eGFR(cr-cys)) also is uncertain.Study designNested case-cohort.Setting & participantsParticipants enrolled in the Osteoporotic Fractures in Men (MrOS) Study (5,994 men aged ≥ 65 years from 6 US centers) including a random subcohort of 1,602 men and 168 men with incident hip fractures (51 of whom were in the subcohort).PredictoreGFR(cys), eGFR(cr), and eGFR(cr-cys) computed using the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) equations and expressed in categories of <60, 60-74, and ≥ 75 mL/min/1.73 m(2) (referent group).OutcomeIncident hip fracture ascertained by participant contacts every 4 months and confirmed with radiographic reports.ResultsMedian eGFR(cys) was 72.9 (IQR, 60.5-85.7) mL/min/1.73 m(2). In unadjusted models, all measures of eGFR were associated with increased hip fracture risk. However, after adjustment for age, race, site, and body mass index, the association of lower eGFR(cys) (but not lower eGFR(cr) or lower eGFR(cr-cys)) with higher hip fracture risk remained: for <60 versus ≥ 75 mL/min/1.73 m(2), HRs were 1.96 [95% CI, 1.25-3.09], 0.84 [95% CI, 0.52-1.37], and 1.08 [95% CI, 0.66-1.77] for eGFR(cys), eGFR(cr), and eGFR(cr-cys), respectively. Similarly, after adjustment for age, race, site, and body mass index, eGFR < 60 mL/min/1.73 m(2) defined by eGFR(cys), but not eGFR(cr) or eGFR(cr-cys), was associated with higher hip fracture risk. The association between eGFR(cys) and hip fracture was not explained by levels of calciotropic hormones or inflammatory markers, but the relationship was attenuated and no longer reached significance (for <60 vs ≥ 75 mL/min/1.73 m(2): HR, 1.43; 95% CI, 0.88-2.34) after consideration of additional clinical risk factors and bone mineral density.LimitationsFindings not generalizable to other populations; residual confounding may exist.ConclusionsOlder community-dwelling men with lower eGFR(cys) have an increased risk of hip fracture that is explained in large part by greater burden of risk factors among men with lower eGFR(cys). In contrast, lower eGFR(cr) or lower eGFR(cr-cys) was not associated with a higher age-adjusted hip fracture risk.

Dataset Information

GFR estimated with creatinine rather than cystatin C is more reflective of the true risk of adverse outcomes with low GFR in kidney transplant recipients.

Background

Methods

Results

Conclusion

Publications

GFR estimated with creatinine rather than cystatin C is more reflective of the true risk of adverse outcomes with low GFR in kidney transplant recipients.

Similar Datasets

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